Summary

• The clinical manifestation of pathological hypercortisolism from any cause.
• Cushing's disease, which is hypercortisolism caused by an ACTH-secreting pituitary adenoma, is the most common cause of Cushing's syndrome, and is responsible for 60% to 70% of cases.
• Though uncommon, the prevalence of endogenous Cushing's syndrome is greater than previously thought.
• It may be difficult to distinguish patients with mild Cushing's syndrome from those with the metabolic syndrome (central obesity with insulin resistance, and hypertension). Features more specific to Cushing's syndrome include proximal muscle weakness, supraclavicular fat pads, facial plethora, violaceous striae, easy bruising, and premature osteoporosis.
• After exclusion of exogenous corticosteroid use, patients with suspected Cushing's syndrome should be tested for hypercortisolism with 1 of 4 high-sensitivity tests (late-night salivary cortisol; 1 mg overnight low-dose dexamethasone suppression testing, 24-hour urinary free cortisol; or 48-hour 2 mg dexamethasone suppression testing).
• At least 1 additional test should be used to confirm hypercortisolism in patients with a positive initial screening test.
• Once endogenous hypercortisolism is confirmed, plasma adrenocorticotropic hormone (ACTH) should be measured. If ACTH is suppressed, diagnostic testing should focus on the adrenal glands. If ACTH is not suppressed, pituitary or ectopic disease should be sought.
• In the vast majority of cases of endogenous Cushing's syndrome, surgical resection of the pituitary adenoma or adrenal adenoma that is causing hypercortisolism is the primary treatment of choice.